Plantago ovata (Psyllium Husk) Ameliorates Streptozotocin-Induced Diabetes in Rats via Modulating Oxidative Stress and the Expression of PPAR-γ, Nrf2, and TNF-α
Keywords:
Plantago ovate; Husk, Antidiabetic; Antioxidant; GC-MS, Docking.Abstract
Background: Plantago ovata (psyllium husk) has untapped potential and is emerging as a promising candidate for diabetes management. Yet, its bioactive properties and underlying mechanisms remain inadequately investigated.
Aim: This study aims to investigate the phytochemical profile, antioxidant capacity, safety, and antidiabetic potential of methanolic Plantago ovata husk extract compared to its crude fibre in streptozotocin (STZ)-induced diabetic rats.
Methods: In vitro characterisation of the phytochemicals and their functional groups using GC–MS and FTIR revealed the presence of phenols, carboxylic acids, alkenes, and fatty acids. The methanolic extract is considered safe and exhibits potent in vitro antioxidant scavenging potential (IC◻◻ = 42.72 mg/ml).
Results: In vivo evaluation of the acute oral toxicity, antihyperglycemic, antihyperlipidemic, antioxidant, liver and kidney function, and antioxidant effects of Plantago ovata husk extract (100 or 200 mg/kg BW) and fibre (0.5 g/kg BW) in STZ-induced diabetic rats manifested a significant decrease in blood glucose, AST, ALT, ALP, urea, and creatinine. Moreover, the antihyperlipidemic action of psyllium husk is evidenced by significant decreases in TG, TC, and LDL levels and a significant increase in HDL levels compared with untreated diabetic rats. Oxidative stress markers significantly improved. Histological alterations of the liver, kidney, and pancreas were examined microscopically. Psyllium husk fibre and extract diminished the detrimental effects of peroxidation on vital organs and sustained tissue integrity. Mechanistic insights were further explored through gene expression and in silico molecular docking studies, suggesting possible modulation of PPAR-γ, Nrf2, TNF, and inhibition of SGLT2.
Conclusion: Plantago ovata husk can serve as a promising antidiabetic and antioxidant pharmaceutical alternative and a talented nucleus for designing supplementary effective and selective therapeutic agents of nutritional origin, especially as an antioxidant and potentially for alleviating diabetes.
References
1. Abdel Aziz, R. L., Hussein, M. M., El-Said, H., Kamel, S., Ibrahim, M. A., and Abdel-Wahab, A. (2023). Monitoring of health status, performance and transcript abundance of some genes in dairy heifers produced by embryo transfer or artificial insemination.
Reprod. Domest. Anim. 58, 1146–1155. doi: 10.1111/rda.14417
2. ABEL, L. L., LEVY, B. B., BRODIE, B. B., and KENDALL, F. E. (1952). A simplified
method for the estimation of total cholesterol in serum and demonstration of its specificity. J. Biol. Chem. 195, 357–366. doi: 10.1016/s0021-9258(19)50907-3
3. Abo El-Ela, F. I., Gamal, A., El-Banna, H. A., Ibrahim, M. A., El-Banna, A. H., Abdel-Razik, A. R. H., et al. (2024). Repro-protective activity of amygdalin and spirulina platensis in niosomes and conventional forms against aluminum chloride–induced testicular challenge in adult rats: role of CYP11A1, StAR, and HSD-3B expressions. Naunyn. Schmiedebergs. Arch. Pharmacol. 397, 3211–3226. doi: 10.1007/s00210-023-02788-9
4. Abouzid, M. R., Ali, K., Elkhawas, I., and Elshafei, S. M. (2022). An Overview of Diabetes Mellitus in Egypt and the Significance of Integrating Preventive Cardiology in Diabetes Management. Cureus 14. doi: 10.7759/cureus.27066
5. Abutair, A. S., Naser, I. A., and Hamed, A. T. (2016). Soluble fibers from psyllium improve glycemic response and body weight among diabetes type 2 patients (randomized control trial). Nutr. J. 15, 1–7. doi: 10.1186/s12937-016-0207-4
6. Ahmed, I., Naeem, M., Shakoor, A., Ahmed, Z., and Iqbal, H. M. N. (2010). Investigation of anti-diabetic and hypocholesterolemic potential of psyllium husk fiber (plantago psyllium) in diabetic and hypercholesterolemic albino rats. World Acad. Sci. Eng.Technol. 37, 1229–1233.
7. Alzamil, H. (2020). Elevated Serum TNF-α Is Related to Obesity in Type 2 Diabetes Mellitus and Is Associated with Glycemic Control and Insulin Resistance. J. Obes. 2020, 5076858. doi: 10.1155/2020/5076858
8. Ansari, A. Q., Ahmed, S. A., Waheed, M. A., and Juned, S. (2013). Extraction and determination of antioxidant activity of Withania somnifera Dunal. Eur J Exp Biol 3, 502–507.
9. Ansari, P., Samia, J. F., Khan, J. T., Rafi, M. R., Rahman, M. S., Rahman, A. B., et al. (2023). Protective Effects of Medicinal Plant-Based Foods against Diabetes: A Review on Pharmacology, Phytochemistry, and Molecular Mechanisms. Nutrients 15. doi: 10.3390/nu15143266
10. Assmann, G., Schriewer, H., Schmitz, G., and Hagele, E. O. (1983). Quantification of high-density-lipoprotein cholesterol by precipitation with phosphotungstic acid/MgCl2. Clin. Chem. 29, 2026–2030. doi: 10.1093/clinchem/29.12.2026
11. BIOVA, D. S. (2023). Enhancing Rational Ligand Design Pharmacophore and Ligand-Based Design With Biovia Discovery Studio ® Datasheet. Available at: www.3ds.com.
12. BIOVIA Discovery Studio Visualizer (n.d.). BIOVIA Discov. Stud. Vis. 24.1.0. Available at: https://www.3ds.com/products-services/biovia/products/molecular-modeling-simulation/biovia-discovery-studio/
13. Brown, T. (2008). Deisign thinking. Harv. Bus. Rev. 86, 84–92. doi: 10.1002/med
14. Brum, J., Ramsey, D., McRorie, J., Bauer, B., and Kopecky, S. L. (2018). Meta-Analysis of Usefulness of Psyllium Fiber as Adjuvant Antilipid Therapy to Enhance Cholesterol Lowering Efficacy of Statins. Am. J. Cardiol. 122, 1169–1174. doi: 10.1016/j.amjcard.2018.06.040
15. Bucolo, G., and David, H. (1973). Quantitative determination of serum triglycerides by the use of enzymes. Clin. Chem. 19, 476–482. doi: 10.1093/clinchem/19.5.476
16. Caturano, A., D’Angelo, M., Mormone, A., Russo, V., Mollica, M. P., Salvatore, T., et al. (2023). Oxidative Stress in Type 2 Diabetes: Impacts from Pathogenesis to Lifestyle Modifications. Curr. Issues Mol. Biol. 45, 6651–6666. doi: 10.3390/cimb45080420
17. Chakraborty, U., and Das, H. (2010). Antidiabetic and Antioxidant Activities of Cinnamomum tamala Leaf Extracts in Stz-Treated Diabetic Rats. 5, 12–18.
18. Cole, J. B., and Florez, J. C. (2020). Genetics of diabetes mellitus and diabetes complications.Nat. Rev. Nephrol. 16, 377–390. doi: 10.1038/s41581-020-0278-5
19. Dallakyan, S., and Olson, A. (2015). Participation in global governance: Coordinating “the voices of those most affected by food insecurity.” Glob. Food Secur. Gov. 1263, 1–11. doi: 10.1007/978-1-4939-2269-7
20. Durak, I., Yurtarslanl, Z., Canbolat, O., and Akyol, Ö. (1993). A methodological approach to superoxide dismutase (SOD) activity assay based on inhibition of nitroblue tetrazolium (NBT) reduction. Clin. Chim. Acta 214, 103–104. doi: 10.1016/0009-8981(93)90307-P
21. Ezhilan, B. P., and Neelamegam, R. (2012). GC-MS analysis of phytocomponents in the ethanol extract of Polygonum chinense L. Pharmacognosy Res. 4, 11–14. doi: 10.4103/0974-8490.91028
22. Feinglos, M. N., Gibb, R. D., Ramsey, D. L., Surwit, R. S., and McRorie, J. W. (2013).Psyllium improves glycemic control in patients with type-2 diabetes mellitus. Bioact. Carbohydrates Diet. Fibre 1, 156–161. doi: 10.1016/j.bcdf.2013.02.003
23. Fernoagă, C., Cornilă, M., and Codreanu, M. (2016). Study on Clinical and Therapeutical Approaching Pets With Diabetes and Obesity. Proc. Rom. Acad., Ser. B 18, 195–200.
24. Foti, M. (2008). Antioxidant properties of phenols. J. Pharm. Pharmacol. 59, 1673–1685. doi: 10.1211/jpp.59.12.0010
25. Friedewald, W. T., Levy, R. I., and Fredrickson, D. S. (1972). Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin. Chem. 18, 499–502. doi: 10.1093/clinchem/18.6.499
26. Gazali, M., Jolanda, O., Husni, A., Adibah, F., and Majid, A. (2023). Green Seaweed Halimeda tuna Extract from the Coast of Lhok.
27. Gholami, Z., Clark, C. C. T., and Paknahad, Z. (2024). The effect of psyllium on fasting blood sugar, HbA1c, HOMA IR, and insulin control: a GRADE-assessed systematic review and meta-analysis of randomized controlled trials. BMC Endocr. Disord. 24, 82. doi: 10.1186/s12902-024-01608-2
28. Giacco, F., and Brownlee, M. (2010). Oxidative stress and diabetic complications. Circ. Res.107, 1058–1070. doi: 10.1161/CIRCRESAHA.110.223545
29. Gulcin, İ., and Alwasel, S. H. (2023). DPPH Radical Scavenging Assay. Processes 11. doi: 10.3390/pr11082248
30. Guo, Q., Cui, S. W., Wang, Q., Goff, H. D., and Smith, A. (2009). Microstructure and rheological properties of psyllium polysaccharide gel. Food Hydrocoll. 23, 1542–1547. doi: 10.1016/J.FOODHYD.2008.10.012
31. Heim, K. E., Tagliaferro, A. R., and Bobilya, D. J. (2002). Flavonoid antioxidants : chemistry metabolism and structure-activity relationships. 13, 572–584.
32. Hiraizumi, M., Akashi, T., Murasaki, K., Kishida, H., Kumanomidou, T., Torimoto, N., et al. (2023). Transport and inhibition mechanism of the human SGLT2-MAP17 glucose transporter. Nat. Struct. Mol. Biol. doi: 10.1038/s41594-023-01134-0
33. Idris, I., and Donnelly, R. (2009). Sodium-glucose co-transporter-2 inhibitors: An emerging new class of oral antidiabetic drug. Diabetes, Obes. Metab. 11, 79–88. doi: 10.1111/j.1463-1326.2008.00982.x
34. Jane, M., McKay, J., and Pal, S. (2019). Effects of daily consumption of psyllium, oat bran and polyGlycopleX on obesity-related disease risk factors: A critical review. Nutrition 57, 84–91. doi: 10.1016/j.nut.2018.05.036
35. Joshi, S., Amatya, S., Pandey, R. D., Khadka, P., and Bhattarai, J. (2020). Antimicrobial, Antioxidant, Antidiabetic, Cytotoxic Activities and GC-MS Analysis of Methanolic Extract of Elaeocarpus sphaericus Leaves from Nepal. www.arcjournals.org Int. J. Adv. Res. Chem. Sci. 8, 11–23. doi: 10.20431/2349-0403.0801002
36. Khedher, A., Dhibi, S., Bouzenna, H., Akermi, S., El Feki, A., Teles, P. H. V., et al. (2022).Antiulcerogenic and antioxidant activities of Plantago ovata ethanolic extract in rats.Braz. J. Biol. 84, e255120. doi: 10.1590/1519-6984.255120
37. KIND, P. R., and KING, E. J. (1954). Estimation of plasma phosphatase by determination of hydrolysed phenol with amino-antipyrine. J. Clin. Pathol. 7, 322–326. doi: 10.1136/jcp.7.4.322
38. Lasalvia, M., Capozzi, V., and Perna, G. (2022). Comparison of FTIR spectra of different breast cell lines to detect spectral biomarkers of pathology. Infrared Phys. Technol. 120, 103976. doi: 10.1016/j.infrared.2021.103976
39. Lippi, U., and Guidi, G. (1970). A new colorimetric ultramicromethod for serum glutamicoxalacetic and glutamic-pyruvic transaminase determination. Clin. Chim. Acta 28, 431–437. doi: 10.1016/0009-8981(70)90069-0
40. List, J. F., and Whaley, J. M. (2011). Glucose dynamics and mechanistic implications of SGLT2 inhibitors in animals and humans. Kidney Int. 79, S20–S27. doi: 10.1038/ki.2010.512
41. Livak, K. J., and Schmittgen, T. D. (2001). Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 25, 402–408. doi: 10.1006/meth.2001.1262
42. Lorke, D. (1983). A new approach to practical acute toxicity testing. Arch. Toxicol. 54, 275–287. doi: 10.1007/BF01234480
43. Molnar, D., Björnson, E., Larsson, M., Adiels, M., Gummesson, A., Bäckhed, F., et al. (2023). Pre-diabetes is associated with attenuation rather than volume of epicardial adipose tissue on computed tomography. Sci. Rep. 13, 1–12. doi: 10.1038/s41598-023-28679-w
44. Ohkawa, H., Ohishi, N., and Yagi, K. (1979). Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal. Biochem. 95, 351–358. doi: 10.1016/0003-2697(79)90738-3
45. Oktay, M., Gülçin, I., and Küfrevioǧlu, Ö. I. (2003). Determination of in vitro antioxidant activity of fennel (Foeniculum vulgare) seed extracts. LWT - Food Sci. Technol. 36, 263–271. doi: 10.1016/S0023-6438(02)00226-8
46. Paglia, D. E., and Valentine, W. N. (1967). Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. J. Lab. Clin. Med. 70, 158–169.
47. Pettersen, E. F., Goddard, T. D., Huang, C. C., Meng, E. C., Couch, G. S., Croll, T. I., et al. (2021). UCSF ChimeraX: Structure visualization for researchers, educators, and developers. Protein Sci. 30, 70–82. doi: 10.1002/pro.3943
48. Rafiee, M., Mortazavi, P., and Asghari, A. (2021). Evaluation of serum alkaline phosphatase changes and TGF- β expression in the liver of cholestatic rats treated with ethanolic extract of Plantago Ovata. Iran. J. Vet. Med. 15, 358–368. doi: 10.22059/IJVM.2020.306770.1005112
49. Rangwala, S. M., and Lazar, M. A. (2004). Peroxisome proliferator-activated receptor gamma in diabetes and metabolism. Trends Pharmacol. Sci. 25, 331–336. doi: 10.1016/j.tips.2004.03.012
50. Sabitha, V., Ramachandran, S., Naveen, K. R., and Panneerselvam, K. (2011). Antidiabetic and antihyperlipidemic potential of Abelmoschus esculentus (L.) Moench. in streptozotocin-induced diabetic rats. J. Pharm. Bioallied Sci. 3, 397–402. doi: 10.4103/0975-7406.84447
51. Sadeer, N. B., Montesano, D., Albrizio, S., Zengin, G., and Mahomoodally, M. F. (2020). The versatility of antioxidant assays in food science and safety—chemistry, applications, strengths, and limitations. Antioxidants 9, 1–39. doi: 10.3390/antiox9080709
52. Saeed, M. A., and Narendran, P. (2014). Dapagliflozin for the treatment of type 2 diabetes: A review of the literature. Drug Des. Devel. Ther. 8, 2493–2505. doi: 10.2147/DDDT.S50963
53. Salau, V. F., Erukainure, O. L., Ibeji, C. U., Koorbanally, N. A., and Islam, M. S. (2020). Umbelliferone stimulates glucose uptake; modulates gluconeogenic and nucleotide-hydrolyzing enzymes activities, and dysregulated lipid metabolic pathways in isolated psoas muscle. J. Funct. Foods 67, 103847. doi: 10.1016/j.jff.2020.103847
54. Salau, V. F., Erukainure, O. L., Koorbanally, N. A., Chukwuma, C. I., and Islam, M. S. (2022). Cinnamic Acid Improves Glucose Uptake and Utilization with Concomitant Improvement of Redox and Bioenergetic Homeostasis, While Modulating Glucose-Lipid Metabolic Switch in Isolated Psoas Muscle. Rev. Bras. Farmacogn. 32, 931–941. doi: 10.1007/s43450-022-00329-8
55. Shapaval, V., Afseth, N. K., Vogt, G., and Kohler, A. (2014). Fourier transform infrared spectroscopy for the prediction of fatty acid profiles in Mucor fungi grown in media with different carbon sources. Microb. Cell Fact. 13, 1–11. doi: 10.1186/1475-2859-13-86
56. Song, Y. Z., Ruan, M., Ye, Y., Li, Y. Y., Xie, W., Shen, J., et al. (2008). Experimental and density functional theory and ab initio Hartree-Fock study on the vibrational spectra of 2-(4-fluorobenzylideneamino)-3-(4-hydroxyphenyl) propanoic acid. Spectrochim. Acta - Part A Mol. Biomol. Spectrosc. 69, 682–687. doi: 10.1016/j.saa.2007.05.059
57. Su, C. H., Hsu, C. H., and Ng, L. T. (2013). Inhibitory potential of fatty acids on key enzymes related to type 2 diabetes. BioFactors 39, 415–421. doi: 10.1002/biof.1082
58. Su, L. J., Zhang, J. H., Gomez, H., Murugan, R., Hong, X., Xu, D., et al. (2019). Reactive Oxygen Species-Induced Lipid Peroxidation in Apoptosis, Autophagy, and Ferroptosis. Oxid. Med. Cell. Longev. 2019. doi: 10.1155/2019/5080843
59. Suhargo, L., Winarni, D., Fatimah, Kharisma, V. D., and Ansori, A. N. M. (2023). Antidiabetic Activity of Daun Wungu (Graptophyllum pictum L. Griff) Extract via Inhibition Mechanism of TNF-α, IL-6, and IL-8: Molecular Docking and Dynamic Study. Res. J. Pharm. Technol. 16, 2291–2296. doi: 10.52711/0974-360X.2023.00376
60. Suvarna, S. K., Layton, C., and Bancroft, J. D. (2018). Bancroft’s Theory and Practice of Histological Techniques, Eighth Edition. doi: 10.1016/C2015-0-00143-5
61. Swaroop, J. J., Rajarajeswari, D., and Naidu, J. N. (2012). Association of TNF-α with insulin resistance in type 2 diabetes mellitus. Indian J. Med. Res. 135, 127–130. doi: 10.4103/0971-5916.93435
62. Talukder, P., Talapatra, S., Ghoshal, N., and Sen Raychaudhuri, S. (2016). Antioxidant activity and high-performance liquid chromatographic analysis of phenolic compounds during in vitro callus culture of Plantago ovata Forsk. and effect of exogenous additives on accumulation of phenolic compounds. J. Sci. Food Agric. 96, 232–244. doi: 10.1002/jsfa.7086
63. Thrasher, J. (2017). Pharmacologic Management of Type 2 Diabetes Mellitus: Available
64. Therapies. Am. J. Cardiol. 120, S4–S16. doi: 10.1016/j.amjcard.2017.05.009 Trinder, P. (1969). Determination of Glucose in Blood Using Glucose Oxidase with an
65. Alternative Oxygen Acceptor. Ann. Clin. Biochem. Int. J. Lab. Med. 6, 24–27. doi: 10.1177/000456326900600108
66. van der Weerd, J., van Loon, A., and Boon, J. J. (2005). FTIR studies of the effects of pigments on the aging of oil. Stud. Conserv. 50, 3–22. doi: 10.1179/sic.2005.50.1.3
67. Verma, A., and Mogra, R. (2013). Psyllium (Plantago ovata) Husk: A Wonder Food for Good Health. Int. J. Sci. Res. ISSN (Online Index Copernicus Value Impact Factor 14, 2319–7064. Available at: www.ijsr.net
68. Villapol, S. (2018). Roles of Peroxisome Proliferator-Activated Receptor Gamma on Brain and Peripheral Inflammation. Cell. Mol. Neurobiol. 38, 121–132. doi: 10.1007/s10571-017-0554-5
69. Wahid, A., Mahmoud, S. M. N., Attia, E. Z., Yousef, A. E. S. A., Okasha, A. M. M., and Soliman, H. A. (2020). Dietary fiber of psyllium husk (Plantago ovata) as a potential antioxidant and hepatoprotective agent against CCl4-induced hepatic damage in rats. South African J. Bot. 130, 208–214. doi: 10.1016/j.sajb.2020.01.007
70. Wanner, C., and Marx, N. (2018). SGLT2 inhibitors: the future for treatment of type 2 diabetes mellitus and other chronic diseases. Diabetologia 61, 2134–2139. doi: 10.1007/s00125-018-4678-z
71. Wood, I. S., and Trayhurn, P. (2003). Glucose transporters (GLUT and SGLT): expanded families of sugar transport proteins. Br. J. Nutr. 89, 3–9. doi: 10.1079/bjn2002763
72. Yamamoto, Y., Narumi, K., Yamagishi, N., Nishi, T., Ito, T., Iseki, K., et al. (2023). Oral administration of linoleic acid immediately before glucose load ameliorates postprandial hyperglycemia. Front. Pharmacol. 14, 1–9. doi: 10.3389/fphar.2023.1197743
73. Younis, I. Y., Khattab, A. R., Selim, N. M., Sobeh, M., Elhawary, S. S., and Bishbishy, M. H. E. (2022). Metabolomics-based profiling of 4 avocado varieties using HPLC–MS/MS and GC/MS and evaluation of their antidiabetic activity. Sci. Rep. 12, 1–15. doi: 10.1038/s41598-022-08479-4
74. Zhou, X., Zhang, W., Liu, X., Zhang, W., and Li, Y. (2015). Interrelationship between diabetes and periodontitis: Role of hyperlipidemia. Arch. Oral Biol. 60, 667–674. doi:
10.1016/J.ARCHORALBIO.2014.11.008
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